This research will be done primarily at Christian Medical College, Vellore, India in collaboration with Dr. Gagandeep Kang as an extension of NIH grant RO1 AI05786, 04/15/03-3/31/08. This application seeks to extend basic laboratory studies on the functional role of the Cpgp40/15 gene and its glycoprotein products gp40 and gp!5 in mediating Cryptosporidium-host cell interactions to a translational study on Cpgp40/15 polymorphisms in clinical isolates and immune response to gpl5 in natural Cryptosporidium spp. infections in children in southern India. The overall goal of studies on cryptosporidiosis in CMC, Vellore is to investigate the molecular epidemiology of cryptosporidiosis and the human immune response to Cryptosporidium spp. in southern India where this parasite is a major cause of diarrhea in children. Cryptosporidial infection in early childhood may result in subsequent impairment in growth, physical fitness and cognitive function. In children with AIDS, this parasite may cause severe and often fatal diarrheal disease for which there is no specific therapy. Very little is known about the molecular epidemiology of cryptosporidiosis or about host immune responses to this parasite, particularly in the setting of the developing world. The focus of this proposal will be on molecular characterization of Cryptosporidium spp isolates based on Cpgp40/15 polymorphisms and on determination of serum antibody responses to gp 15 in children aged 0 to 24 months of age who are enrolled in an ongoing birth cohort study in an urban slum area of southern India. This study will enable future studies to determine whether Cpgp40/15 polymorphisms and antibody response to gp!5 can be used as tools to study the epidemiology of cryptosporidiosis in developing countries, to determine the role of gp!5 in human infection and to evaluate whether immune responses to this protein is involved in protection from disease. In the first specific aim Cpgp40/15 allelic subgroups of Cryptosporidium spp isolates from children with cryptosporidiosis in southern India will be determined. In the second specific aim serum IgG, IgM and IgA and fecal secretory IgA levels to gp!5 will be measured in Cryptosporidium spp infected children and in children with no detectable Cryptosporidium spp infection and the change in antibody levels during the study period determined.